Background: Ovarian cancer has been named "the silent killer" because it frequently causes non-specific symptoms which contribute to diagnostic delay. Despite of the improved surgical techniques and effective chemotherapeutic regimens available for management of ovarian cancer, there is no improvement in its early detection. Thus, ovarian cancer remains a leading cause of death from gynecological malignancies with an overall poor prognosis. The identification of novel cancer biomarker opens the possibility for early detection, and better monitoring of tumor progression. Haptoglobin is a novel biomarker which was used in diagnosis in ovarian cancer. Objectives: To assess the performance of haptoglobin and CA125 to increase the sensitivity and specificity in diagnosis of nature of ovarian mass.    Patients and Methods: This study was carried out on 90 women attending at Al-Hussein and Bab El-Sha'aria University Hospitals. A prospective study was held on patients with ovarian mass prepared for surgery. It was a case control study. It incorporated on 60 patients with ovarian masses (30 women with benign ovarian masses and 30 women with malignant ovarian masses), and 30 women without masses (control group). Those patients were subjected to careful history taking, clinical examination, ultrasound examination and preoperative assessment of serum levels of Haptoglobin and CA125. Results: the prediction of CA-125 was better than that of haptoglobin but the combination of both markers was better than the prediction of one of them in diagnosis of ovarian cancer. Conclusion: Haptoglobin has an important role in the prediction of ovarian cancer. It increased significantly in malignant ovarian tumors than in benign ovarian tumors. So, it can be used as a diagnostic tumor marker in cases of ovarian neoplasia.